Current Pharmaceutical Biotechnology - Online First

Ropivacaine (RPV), a commonly used local anesthetic, is limited in its effectiveness for postoperative pain management due to its short duration of action. To address this issue, this study further explores the development of poly(lactic-co-glycolic) acid (PLGA)-PVA nanocarriers designed to extend RPV's release and efficacy.

PLGA-PVA-RPV nanocarriers were synthesized via an emulsion technique and comprehensively characterized using transmission scanning electron microscopy, Malvern ZS90, and Fourier transform infrared spectroscopy. The cytotoxicity of these nanocarriers against HaCaT cells was determined using the Cell Counting Kit-8 viability assay and calcein-acetoxymethyl/ propidium iodide staining. Flow cytometry and scratch assays were used to assess their effects on the HaCaT cell cycle, apoptosis, and migration.

The PLGA-PVA-RPV nanocarriers exhibited a spherical morphology, small size (10.90 ± 2.19 nm), uniform distribution, and stable zeta potential (−7.93 ± 0.81 mV). The PLGA-PVA-RPV nanoparticles demonstrate excellent biocompatibility; even at a high concentration of 1000 μg/mL, the cell viability remains above 80%, which is significantly higher than that of the free RPV group (67.3%, P < 0.05). Further mechanistic studies showed that PLGA-PVA-RPV nanoparticles induced cell cycle arrest and inhibited cell migration, collectively demonstrating their low toxicity, excellent biocompatibility, and sustained-release potential.

The PLGA-PVA-RPV nanocarriers demonstrate enhanced efficacy and biocompatibility for prolonged ropivacaine release, offering a promising strategy for postoperative pain management. Future work should focus on in vivo validation and parameter optimization to facilitate clinical translation.

PLGA-PVA-RPV nanocarriers possess optimal physicochemical properties (small size, homogeneity, stability) and superior biosafety, providing a promising strategy for extending RPV's analgesic efficacy. This technology has significant potential to improve postoperative pain management.

Dihydromyricetin (DMY), a phytoflavonoid with diverse pharmacological activities, is limited in cosmetic applications by poor solubility, easy discoloration, and low bioavailability. This study aimed to address these drawbacks for its practical cosmetic use.

DMY nanoliposomes (DMY-NL) were prepared via ethanol injection-high-pressure homogenization, with orthogonal tests optimizing the process using particle size, PDI, and zeta potential as indices. Tests included in vitro dialysis-based sustained-release assay, erythrocyte hemolysis/human patch tests (safety), and DPPH scavenging/hemolysis/human patch anti-irritation tests (soothing efficacy).

DMY-NL had >90% encapsulation efficiency, 90-day stability under different storage conditions, and 48-h sustained release (superior to control). Safety was confirmed by hemolysis and patch tests; soothing efficacy was verified via DPPH scavenging and anti-irritation tests.

DMY-NL’s high encapsulation, good stability, and sustained release solve DMY’s cosmetic application limitations. Confirmed safety and soothing effects support its practical use in cosmetics.

This study provides a theoretical and practical basis for DMY’s cosmetic application, expected to expand its use in the cosmetic industry.

Neurodegenerative diseases are a group of life-threatening conditions characterized by gradual and severe neuronal degeneration, posing a significant global health challenge. Many neurodegenerative diseases, including Alzheimer's disease and Parkinson’s disease, share identical and recognizable etiologies, such as neuronal degeneration, apoptosis, oxidative stress, lipid peroxidation, Ca²⁺ overload, neuroinflammation, protein aggregation, endoplasmic reticulum stress, and mitochondrial dysfunction. Among these etiologies, oxidative stress and mitochondrial dysfunction are the primary contributing factors, involving several enzymes and signaling molecules in the underlying mechanism of disease progression. Globally available treatments provide only temporary symptomatic relief with side effects, and yet there is no medication to eradicate the disease-related cause.

Extensive research has explored novel herbal medications offered as neuroprotective against these debilitating conditions, aiming to reverse or halt the disease progression with minimal adverse effects. Pinostrobin is a major bioactive flavonoid primarily isolated from Boesenbergia rotunda (Fingerroot). Established research has reported that pinostrobin exhibits a wide array of pharmacological activities, including anti-inflammatory, anti-leukemia, antioxidant, antimicrobial properties, as well as protective effects against mitochondrial dysfunction and neurodegeneration.

Based on preclinical studies, we have summarised the current knowledge of pinostrobin's neuroprotective actions, highlighting its effectiveness in mitigating neuronal damage, preserving synaptic function, reducing oxidative stress, neuroinflammation, protein aggregation, mitochondrial apoptosis, and calcium overload. These mechanisms collectively support its therapeutic potential in modulating the molecular pathways underlying Alzheimer’s and Parkinson’s disease.

This review offers a comprehensive analysis of pinostrobin and its molecular pathways in combating neurodegenerative diseases, highlighting its promising effectiveness as a natural neuroprotective agent in Alzheimer’s and Parkinson’s disease by modulating mitochondrial and oxidative stress-mediated pathways.

Ganoderma lucidum is considered a medicinal mushroom, as it primarily improves gut health by modulating the gut microbiota. As an abundant source of bioactive metabolites, antioxidants, and industrial enzymes, mushrooms make significant contributions to functional foods, nutrition, and pharmaceuticals. Polysaccharides derived from G. lucidum exhibit prebiotic potential, promoting the growth and activity of beneficial gut microorganisms.

This systematic review examines the impact of white rot basidiomycetes metabolites on colorectal cancer treatment. We have compiled and analyzed data from PubMed, Google Scholar, and ResearchGate, presenting a comprehensive report with a table for clear understanding.

Evidence from in vivo and in vitro studies demonstrates that G. lucidum has potential as a gastrointestinal cancer inhibitor by inducing pro-apoptosis, autophagy, G0/G1 cell cycle arrest, and immunomodulation.

Bioactive metabolites and polysaccharides have prebiotic potential, enhancing the growth and activity of beneficial gut microorganisms that may lower the risk of gastrointestinal cancers by modifying gut bacteria. The prebiotic properties may boost immunity, reduce inflammation, and strengthen intestinal barrier integrity.

The current review explores the therapeutic potential of G. lucidum and other medicinal mushrooms as dietary supplements, focusing on their impact on the gut microbiome and gastrointestinal cancer.

Generalized anxiety disorder (GAD) is a prevalent and intricate mental disorder that significantly impairs the quality of life of patients. Currently, the exact etiology of GAD remains incompletely understood. Consequently, the discovery of novel drug targets for GAD is highly important.

We obtained cis-eQTL data of druggable genes from the eQTLGen Consortium as the exposure data and GWAS data of GAD from the FinnGen Database as the outcome. The impact of druggable genes on GAD was simulated through Mendelian randomization analysis. Subsequently, a colocalization analysis was conducted to calculate the probability of shared pathogenic variants between the cis-eQTLs of druggable genes and GAD. To further validate our findings, a summary data-based Mendelian randomization (SMR) analysis was carried out.

Mendelian randomization (MR) analysis identified 24 druggable genes with potential causal relationships, among which genetically predicted increased KDM5A levels were associated with a higher risk of GAD (OR=1.0991, 95% CI: 1.0021–1.2056, P=0.0451), suggesting a potential role of KDM5A gene expression in the pathogenesis of GAD. The GAD and KDM5A genes might share a causal variant. The SMR further verified the accuracy of the KDM5A gene.

MR analysis identified KDM5A as a promising therapeutic target for GAD, with additional potential from genes, like MERTK and PPT1. However, the effectiveness of the relevant drug targets requires further validation.

This study suggested that the KDM5A gene might be a potential therapeutic target for treating GAD, providing a direction for future drug development in GAD patients.

The current pharmaceutical industry has increasingly adopted artificial intelligence (AI), integrating it across the entire industrial chain. While AI improves efficiency and reduces costs, it also faces challenges. This study explores both the technological evolution and contemporary innovation hotspots of AI in pharmacy.

This study adopts a fusion analysis of multi-source data, constructing a bi-dimensional analytical framework based on patented inventions (1990-2024) and research articles (2020-2024) as research objects. The study applies the Latent Dirichlet Allocation (LDA) topic model to analyze the evolution of patent topics and employs CiteSpace to construct keyword knowledge graphs from research articles. By integrating patent and article data to define technical labels, the study identifies research hotspots from the perspective of the pharmaceutical life cycle, enabling cross-validation from both scientific and technical dimensions.

The number of AI-related patents in the pharmaceutical field has grown rapidly over the past five years. Technological topics exhibit a distinct evolutionary trend. Research hotspots span the entire pharmaceutical life cycle, from drug development to clinical delivery. Additionally, potential directions for future technological development have been identified.

Research hotspots in the application of AI in pharmaceuticals include target identification, virtual screening, drug delivery, clinical trials, and pharmacovigilance. Precision medicine and explainable AI (XAI)-driven pharmacy modeling are expected to emerge as key directions for future technological development.

AI has already reshaped the pharmaceutical industry through applications across all stages of the pharmaceutical life cycle. It is poised to attract growing research attention and drive innovative applications in the years ahead.

FLRCC is a rare renal carcinoma subtype caused by FH mutations, categorized into hereditary (germline mutations) and sporadic (somatic mutations) forms. These forms are clinically and pathologically similar, complicating differentiation without genetic testing. The aim of this study is to investigate the clinicopathological and molecular genetic differences between hereditary and sporadic fumarate hydratase (FH)-deficient leiomyomatosis and renal cell carcinoma (FLRCC) to improve diagnostic accuracy and clinical management.

A retrospective analysis of 14 FLRCC patients was conducted(May 2020-August 2023). Immunohistochemistry (FH, 2SC, p16), HE staining, and next-generation sequencing (NGS) of tumor tissues and blood leukocytes were performed.

The 14 patients with FH-deficient leiomyoma were 25-54 years old, with a mean age of 36.21 ± 8.16. 78.5% (11/14) had clinical symptoms and multiple, large-sized fibroids (median maximum volume was 75 mm). Patients with leiomyoma and FH deficiency were divided into hereditary and sporadic FLRCC based on FH gene sequencing. Patients with HLRCC had an earlier onset, and the serum tumor marker CA125 was more significant. Moreover, tumor tissues from patients with hereditary and sporadic FH-deficient LRCC differed in immunohistochemical and HE staining characteristics, including more positive p16 and greater susceptibility to invasion and metastasis in patients with HLRCC, as well as malignant proliferation in patients with sporadic FH-deficient LRCC.

Although limited by sample size, our preliminary findings indicated subtle differences in the age of onset, as well as immunohistochemical and histopathological features of hereditary and sporadic FH-deficient LRCC, facilitating the understanding and clinical diagnosis of FLRCC.

In clinical diagnosis, all information should be fully integrated, and a comprehensive judgment should be made to make a correct pathological diagnosis and provide targeted treatment for patients with an FH gene mutation.